Cellular Control 6.1.1 Flashcards
What is a gene mutation
A change in the base sequence of DNA molecule that may result in an altered polypeptide
When do these gene mutations occur?
During S phase of DNA replication
Gene mutations are more likely to occur when:
If You are exposed to mutagenic agents which can interfere with DNA replication
Give a few examples of mutagenic agents.
-high energy radiation (UV light)
-ionising radiation (Gamma rays + X-rays )
-chemicals (carcinogens e.g. mustard gas, cigarette smoke)
What can a gene mutation lead to?
Could result in either:
-a base being deleted or substituted for a different one
This is the regional DNA sequence=
TAC CCA AGT GGC
What type of mutation is this? 1
TAC ACA AGT GGC
What type of mutation is this? 2
TAC CAA GTG GC
- Base substitution mutation
- Base deletion mutation (frameshift)
What is a base substitution mutation ?
-gene mutation
-one nucleotide is incorrectly swapped during DNA replication for another nucleotide
-the correct nucleotide is replaced with an alternative nucleotide
-effects are small
Why might base substitution be considered silent?
Meaning that the new codon still codes for the same amino acid- this is because genetic code is degenerate ( multiple codons can code for the same amino acid) so no change in the sequence and so polypeptide chain likely wont be affected
What is a base deletion mutation?
-gene mutation
-a nucleotide is skipped/absent from the replicated strand
-causes frameshift mutation
-effects can be damaging
Frameshift mutation= removal of one base changes all of the subsequent codons
-more harmful as multiple amino acids may be incorrectly coded for
What is insertion mutation?
-gene mutation
-an extra nucleotide (with a new base) is randomly incorporated into the DNA sequence during replication
Define gene
Section of DNA, coding for a polypeptide
What is a chromosomal mutation?
A change in the structure or or number of chromosomes which can alter the genetic code
What is a mutation?
- a random change in the quantity or structure of the DNA of an organism
-it can happen in the body (somatic) or reproductive cells (germ-line)
What is a point mutation/substitution?
Occurs when one base pair is replaced by another
Mutations occur:
Spontaneously and continuously
Why do mutations usually not have an effect on us?
-as most mutations do not alter the polypeptide or only alter it slightly so that its structure or function is not changed (as the genetic code is degenerate I.e. several different triplets often code for the same amino acid)
-Many mutations occur in non-coding sections of DNA and so have no effect on the amino acid sequence at all
An insertion mutation changes the _________ that would have been coded for by the ___________ ____ _______, as it creates a ___, different triplet of _____.
An insertion mutation changes the amino acid that would have been coded for by the original base triplet as it creates a new different triplet of bases
How does a mutation lead to a change in the polypeptide?
-DNA base sequence determines the sequence of amino acids that make up a protein
-mutation in a gene can lead to a change in the base sequence
-and consequently the amino acids that are coded for
- If these amino acids change then the polypeptide and so protein will change in terms of structure or function
Substitution mutations can take 3 forms:
- Silent mutation
- Missense mutation
- Nonsense mutations
What is a silent mutation?
-no change to the primary structure of the polypeptide despite a change in the nucleotide base as it does not alter the amino acid sequence
In a silent mutation why does a change in the base sequence not lead to a change in the polypeptide?
Because DNA is degenerate and certain codons may code for the same amino acid, leading to no change in the amino acid sequence and therefore no change to the primary structure of the polypeptide
What is a missense substitution mutation?
The mutation alters a single amino acid in the polypeptide chain
Give an example of a disease caused by a single substitution mutation changing a single amino acid in the sequence
Sickle cell anaemia
What is a nonsense mutation?
-mutation creates a premature stop codon
What is a stop codon and its function?
Signal for the cell to stop translation of the mRNA molecule into an amino acid sequence
How does the stop codon affect the polypeptide chain or protein?
Signal for the cell to stop translation of mRNA molecule into an amino acid sequence, causing the polypeptide chain produced to be incomplete and therefore affecting the final protein structure and function
Produce shorter polypeptide chain—> likely to fold differently (depending on how early in the sequence)—-> functionality of protein likely to change
Give an example of a disease caused by a non-sense mutation
Cystic fibrosis- although it not always just only caused by a non-sense mutation
What is a frameshift mutation?
-complete change to the entire amino acid sequence of a protein after the mutation site
-because of the way the translated mRNA is read by the ribosomes
-mRNA is read in codons, groups of 3 nucleotides
-if an additional 1 or 2 nucleotides are added or removed the sequence is ‘shifted’
-translation machinery cannot know that there has been an error, and still reads the sequence in triplet codons
-the entire mRNA and resulting protein are therefore completely different in terms of structure and/or function
In terms of the effects of mutation, what different effects of gene mutations can you have?
-Beneficial mutations
-Harmful mutations
-Neutral mutations
What do we mean by a beneficial mutation?
-alteration to a polypeptide may result in an altered characteristic or function in an organism that causes beneficial effects e.g. enhanced function of a protein
Give an example of each of the following:
-beneficial mutation
-harmful mutation
-neutral/causes of mutations
-Beneficial= rare but often leads to evolution, an example is production of the pigment melanin
-Harmful= cancer, genetic diseases haemophilia, sickle cell anaemia, cystic fibrosis
-Neutral mutation= no effect, e.g.the ability to taste a bitter-tasting chemical found in Brussels sprouts
What is a harmful mutation??
-alteration in the polypeptide may result in an altered characteristic in an organism that causes harmful mutation e.g. malfunctioning of a protein made
Explain how Cystic fibrosis is an example of a deletion mutation?
-in aroun 70%= the mutation that causes disease is deletion mutation
-of 3 nucleotides in the gene coding for the protein CFTR
-the loss of function of CFTR protein caused by this deletion mutation results in symptoms e.g. lung and pancreatic problems as a result of extremely thickened mucus
Explain how a mutation can be neutral and have no effect?
-mutation might not alter the polypeptide
-mutation may alter polypeptide slightly so its structure and function is not changed
-mutation alters structure/function of polypeptide but resulting difference in characteristic provides no particular adv/disadv to the organism
What are insertion and deletions?
Frameshift mutation
Insertion and deletion causes frameshift mutation. What is frameshift mutation?
-disrupts triplet code reading
-every codon after mutation affected
-protein will have diff sequence of amino acids
-so a diff tertiary structure
-t/f protein no longer performs correct/ same function
Significance of genetic code being degenerate on mutations
-Multiple codons code for particular amino acid
-point mutation may have no effect
-make same protein for normal functioning
How does a missense substitution mutation affect the protein?
Change to primary structure ——-> change to tertiary structure & overall 3D shape of protein——-> functionality of protein likely to change
What happens to reading frame when frameshift mutation occurs?
Reading frame now lines up different triplets after point of mutation, genetic code is non-overlapping & each base is only read once
What are chromosomal mutations?
Large sections of chromosomes altered
What is a chromosomal deletion mutation??
Sections of chromosome deleted
What is a chromosomal duplication mutation?
Sections of chromosome (or entire chromosome) duplicated
What is a chromosomal translocation mutation?
Section of chromosome joins another non-homologous chromosome
What is a chromosomal inversion mutation?
Section of chromosome turned upside down
What are the different levels of control?
- Transcriptional- turning genes o/off- DNA more tightly wound around histone proteins during cell division
- Post-Transcriptional- editing RNA
- Translational- turning translation on/off
- Post-translational- editing protein
Evaluate whether a base deletion mutation has a bigger effect on polypeptide structure than a base substitution mutation?
-sub can result in a silent mutation+ no change to primary structure
-sub only changes a single amino acid
-sub does not change the no. Of amino acids whereas deletion reduces by 3
-deletions are frameshift mutation, every amino acid downstream of mutation changes
-however sub can change codon to a stop and if this occurs near the start of the sequence, impact is significant
Why can substitution mutations can be silent?
Because genetic code is degenerate
What is gene regulation?
The control of gene expression
The nucleus of every cell in the human body contains the _____ genes. However not every gene is_________ in every cell. In addition not all genes are expressed ____ the times.
a) same
b)expressed
c)all
What are regulatory mechanisms?
Several mechanisms which exist within cells to make sure the correct genes are expressed in the correct cell at the correct times
What are the types of regulatory mechanisms/levels of control?
Transcriptional
Post transcriptional
Translational
Post translational
What is a structural gene?
Codes for any RNA or protein that has a function within cell e.g. enzymes, membrane carriers, hormones etc.)
-makes any protein product other than a regulatory factor
What is a regulatory gene?
code for proteins (or various forms of RNA) that control the expression of structural genes
-the product of these genes control the expression of structural genes
If the ________ genes being controlled are in any way are involved in the process of transcription, then gene ________ is occurring at the ___________ level.
If the structural genes being controlled are in any way are involved in the process of transcription, then gene control is occurring at the transcriptional level.
Movement of transcription factors
-transcription of a gene will only occur when a molecule from the cytoplasm enters the nucleus and binds to the DNA in the nucleus
What is a transcription factor?
protein molecules which can each bind to different complimentary base sequences on DNA and therefore initiate or inhibit transcription of genes- to control protein synthesis
What happens when a transcription factor is bound to a complimentary base sequence on DNA
Once bound transcription begins, creating the mRNA molecule for that gene which can then be translated in the cytoplasm to create the protein
Without the binding of a transcription factor the…
the gene is inactive and the protein wont be made
How can the rate of transcription be changed?
Transcription factors can either initiate or inhibit transcription and therefore controlling protein synthesis—–> can turn on/off genes so only certain proteins are produced in a particular cell
What enables genes to become specialized in a cell?
-turning on/off particular genes in a cell is what enables them to become specialized
What is the transcriptional level of gene expression?
-transcription regulatory factors bind to DNA near structural genes to switch genes on (activator) or off (repressor) by:
-altering conditions to allow RNA polymerase to bind
(e.g. a transcription factor binding to the promoter region of a gene which allows RNA polymerase to bind and for transcription to occur )
—>prokaryotes= lac operon
—>eukaryotes=modification of histone proteins for chromatin remodeling
-regulation of gene expression during mRNA production- by altering the rate of transcription of genes
Faster rate of transcription= more protein made
Slower rate of transcription= less protein made
-
What is heterochromatin?
tightly wound DNA in cell division e.g. in Prophase, can be seen as chromosomes
How do we get transcription to occur from heterochromatin?
We form a euchromatin by acetylation or phosphorylation
-addition of acetyl groups decreases positivity of histones
-they are less attracted to phosphate on DNA
-DNA and histones weakly associate
-histone acetylation results in loose packing of nucleosomes
-transcription factors can bind to the DNA and genes are expressed
Describe the process of acetylation?
-addition of acetyl groups decreases positivity of histones
-they are less attracted to phosphate on DNA
-DNA and histones weakly associate
-histone acetylation results in loose packing of nucleosomes
-transcription factors can bind to the DNA and genes are expressed
What is euchromatin?
loosely wound DNA in cell division e.g. in interphase, can’t be seen as chromosomes
What is a chromatin?
Is the DNA in our cells along with the proteins associated with it called Histones
Why can transcription only occur in euchromatin?
because there’s space for RNA polymerase to attach to the promoter region
How to form heterochromatin from euchromatin?
methylation—-> increases hydrophobic nature of histones
Define epigenetics
-a heritable change in gene function without changing the DNA base sequence
-caused by the environment
-can inhibit transcription
What two types of epigenetics prevent transcription?
-increased methylation
-decreased acetylation of histones